125 research outputs found
Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY
© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes
of Health, an American Heart Association Predoctoral Fellowship
(J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a
National Science Foundation Predoctoral Fellowship (B.B.)
Acute myeloid leukemia following etoposide therapy for EBV-associated hemophagocytic lymphohistiocytosis: a case report and a brief review of the literature
Angiotensin II type 1 receptor expression in human coronary arteries with variable degrees of atherosclerosis
Autopsy specimens of human coronary arteries were collected from 65 men and women ranging in age from 40–76 years of age. We made 209 coronary artery sections, which were graded in terms of severity of atherosclerosis by means of the Stary classification. Sections were stained using an antibody directed against the angiotensin II type 1 (AT1) receptor. We found that in non-atherosclerotic sections, staining was confined to vascular smooth muscle cells in the media. However, with the advent of atherosclerosis, AT1 receptor expression was also present in atherosclerotic plaque and involved other cell types including inflammatory cells and myofibroblasts. We identified a remarkable correlation between AT1 receptor staining and the severity of coronary atherosclerosis as well as intima-media thickness. These human data correspond well to animal models of atherosclerosis indicating an upregulation of AT1 receptor expression in atherosclerotic tissue
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